Studies in this laboratory are designed to elucidate the role of DNA repair processes in carcinogenesis and in neurodegeneration. We have developed an experimental test for Alzheimer's disease (AD) which has opened a new pathway to its diagnosis and prevention. The new test correctly pinpointed cells donated by all 27 AD patients in the study. In contrast, the test produced negative results in cells from 28 of 31 healthy donors. The test was also negative when used with cells from 10 of 11 donors with other neurodegenerative diseases, such as Parkinson's disease and Huntington's disease. The test could prove useful in supporting, or rendering unlikely, the diagnosis of AD in patients suspected of having it and could also predict inheritance of AD in families with a high prevalence of the disease. The cells studied were from patients with different types of AD - - the early onset, inherited form and the much more common form that occurs among older people in the general population. The test proved accurate in both types. Results were also positive in three persons in an AD family who did not have symptoms of disease when the cells were obtained, although they later developed the disease. In addition, 12 patients with Down's syndrome, who always develop AD as they age, had positive tests. The new laboratory test singles out AD cells apparently by identifying a defect in their ability to repair DNA damage. Blood and skin cells from AD patients are irradiated with intense doses of fluorescent light, which inflicts a certain kind of DNA damage under laboratory conditions. The cells were then treated with chemicals, making it possible to see how much damage had gone unrepaired. The AD and Down's syndrome cells had signs of unrepaired DNA in marked contrast to cells from most healthy donors. The DNA damage in the AD cells was prevented by adding an antioxidant called theaflavin mixture to the cell culture while it was being irradiated with fluorescent light. This finding supports the hypothesis that antioxidants may prevent or slow the progression of AD. This study grew out of work on xeroderma pigmentosum (XP), an inherited disease in which cells are unable to conduct repair of DNA. People with this condition are at a very high risk of skin cancers, and some also experience degeneration of the nervous system which results from the patient's defect in DNA repair. Studies were continued investigating the relationship between defective DNA repair and cancer in patients with XP, Cockayne syndrome, and the XP-Cockayne syndrome complex.